With the complete human genome sequence information, we are faced with the enormous challenge of deciphering its function in relation to understanding the biology of human development health and disease. Protein coding sequences account for less than 2% of the human genome. Cross species sequence comparisons have revealed many conserved non-coding elements (CNEs) throughout the vertebrate genome, most of which are likely to have important functions that are currently un-defined. The goal of this project is to systematically identify and functionally analyze CNEs in the zebrafish Danio rerio, a vertebrate model organism that is not only good for forward genetics but also suitable for large-scale functional analysis. The proposed study will not only provide insights into transcriptional regulation of vertebrate brain development, the methodology developed in this study can also be applied to functionally define CNEs for other developmental processes of interest. [unreadable] [unreadable]